cis- and trans-Acting Factors Influence Expression of the norM-Encoded Efflux Pump of Neisseria gonorrhoeae and Levels of Gonococcal Susceptibility to Substrate Antimicrobials.
cis- and trans-Acting Factors Influence Expression of the norM-Encoded Efflux Pump of Neisseria gonorrhoeae and Levels of Gonococcal Susceptibility to Substrate Antimicrobials.
复制标题
顺式和反式作用因子影响淋球菌正编码外排泵的表达和淋球菌对底物抗菌药物的敏感性水平。
DOI:
10.1128/aac.00821-18
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发表时间:
2018
影响因子:
4.9
通讯作者:
Shafer,WilliamM
中科院分区:
文献类型:
--
作者:
Rouquette-Loughlin,CorinneE;Dhulipala,Vijaya;Reimche,JenniferL;Raterman,Erica;Begum,AfrinA;Jerse,AnnE;Shafer,WilliamM
The gonococcal NorM efflux pump exports substrates with a cationic moiety, including quaternary ammonium compounds such as berberine (BE) and ethidium bromide (EB) as well as antibiotics such as ciprofloxacin and solithromycin. ThenorMgene is part of a four-gene operon that is transcribed from a promoter containing a polynucleotide tract of 6 or 7 thymidines (T's) between the −10 and −35 hexamers; the majority of gonococcal strains analyzed in this study contained a T-6 sequence. Primer extension analysis showed that regardless of the length of the poly(T) tract, the same transcriptional start site (TSS) was used for expression ofnorM. Interestingly, the T-6 tract correlated with a higher level of bothnorMexpression and gonococcal resistance to NorM substrates BE and EB. Analysis of expression of genes downstream ofnorMshowed that the product of thetetR-like gene has the capacity to activate expression ofnorMas well asmurB, which encodes an acetylenolpyroylglucosamine reductase predicted to be involved in the early steps of peptidoglycan synthesis. Moreover, loss of the TetR-like transcriptional regulator modestly increased gonococcal susceptibility to NorM substrates EB and BE. We conclude that bothcis- andtrans-acting regulatory systems can regulate expression of thenorMoperon and influence levels of gonococcal susceptibility to antimicrobials exported by NorM.